The present invention is directed to devices for electrically picking up and dispensing electrically charged powders or beads in a spatially resolved manner. Specifically, this disclosure describes novel electrode configurations and control circuits, and operation and fabrication techniques for electrostatic chucks that pick up, manipulate, transport, and then discharge or place, particles, beads, powders, or objects for use in creating pharmaceutical or chemical compositions, or in performing assays or chemical analysis. The invention solves certain problems associated with sensing chucks that perform powder deposition sensing, by providing a way to cancel error-producing effects when trying to measure accumulated charge with ionic or high polarizability materials in the vicinity of chuck sensing electrodes. Although emphasis is placed on charge sensing chucks that are tailored for powder deposition sensing and calibration, the techniques given may be applied to improve all electrostatic chucks that perform manipulations and/or provide electric fields to aid in moving, switching, shifting or manipulating beads from an originating electrode or source location to a target electrode or location.
Electrostatic chucks can be used to pick up, manipulate, transport, and then discharge or place powders, beads or objects for use in creating pharmaceutical or chemical compositions, or in performing assays or chemical analysis.
Electrostatic chucks operate by acting as clamps to hold or retain an object or objects, and can provide superior performance for manipulating particles or synthetic beads having typical diameters of 100-300 microns in chemical synthesis, such as combinatorial chemistry for solid phase synthesis, or in an assay using PCR (polymerase chain reaction) or other processes. In combinatorial chemistry, a multi-well array such as a microtiter plate allows screening or synthesis of many compounds simultaneously.
For example, electrostatic chucks allow deposition of beads on an array in a manner that is faster and more reliable than by the use of micropipettes. Another application for electrostatic chucks is synthesis of pharmaceutical compositions, especially when used to combine compounds to form compositions to be packaged into administration forms for humans or animals.
Aggregated particles containing one or more active ingredients can be deposited onto well known carriers or substrates to make pharmaceutical dosage forms. Such particles can take the form, for example, of [1] a powders or aerosols, such as dry micronized forms made by air jet milling processes, where overall particle dimensions can be, for example, in the 1 to 10 micron range useful for dry powder respiratory administration of medicaments, with 4-8 microns preferred; [2] beads or microspheres; [3] extremely small structures, including fullerenes, chelates, or nanotubes; or [4] liposomes and fatty droplets formed from lipids or cell membranes; and the like.
The use of electrostatic chucks provides a customized and precise method for formulating drug compositions. The chuck can be used when merging adjacent substrates carrying active ingredient to form multidosage packs, in which dosage can decrease or increase from one individual unit to the next, as in hormone-based (e.g., birth control) drugs or antibiotic remedies. Using electrostatic chucks with deposition sensing, dosages can be established or determined by the number and/or type of beads or amount of powder or particles dispensed onto each pharmaceutical carrier, or by using, separate or external electrical, optical, or mechanical dosage sensing. Using electrostatic chucks to place active ingredients into pharmaceutical compositions can achieve high repeatability and is also advantageous when the active ingredients are not compatible, such as when the active ingredient is poorly soluble with a carrier, or where a formulation or carrier negatively affects the bioavailability of the active ingredient.
Although emphasis is placed in this disclosure on use of electrostatic transporter chucks that apply electric fields for particle retention and/or release, the teachings given here can be applied to chucks that also use other phenomena, such as the use of compressed gas or vacuum, or electrically/chemically switchable adhesives, in controlling particles/or substrates. Electrostatic or quasi-electrostatic holding mechanisms, however, are far more benign to delicate bead or particle structures than traditional mechanical techniques, particularly when manipulating biologically active compounds where crushing, contamination, or oxidative damage is preferably minimized or eliminated.
Typically, particles to be transported or manipulated are tribo-charged through frictional encounters and collisions with tribocharging, substances, charged by induction charging, or charged by corona charging.
Some electrostatic chucks offer precision in being able to have one, and only one bead or particle attracted, transported, and discharged per chuck, or for each well, pixel, or individual spatial element of the electrostatic chuck. Often, each pixel can be considered a tiny electrostatic chuck that is selectively and independently controlled, such as planar chucks having individually addressable x and y coordinates. This includes individually addressable pixels for different (multiple) bead or particle types.
Often, instead of depositing particles or beads singly, electrostatic chucks are used to attract and place a plurality of powder particles, containing active ingredient, on a substrate, such an edible substrate used for pharmaceutical dosage forms.
Electrodes used for attracting beads can vary widely in construction and structure. Particle attracting electrodes, can, for example, be directly exposed, or covered by a dielectric, to prevent ionic breakdown (sparking) in air and to make use of the properties of dielectrics to enhance bead charge holding capacity. To control the amount of charged particles that may be attracted, an indirect method can also be used where a particle attraction electrode attracts particles indirectly, using capacitive coupling to a pad or floating electrode. The instant invention may be applied to any number of electrostatic chuck designs, but to illustrate, simple chucks are shown here to attract particles directly by way of one or more directly biased (non-floating) electrodes.
Devices or methods that can be used with various aspects of the present invention include, for example, the methods for use of transporter chucks, acoustic bead dispensers and other particle-manipulating devices set forth in Sun, xe2x80x9cChucks and Methods for Positioning Multiple Objects on a Substrate,xe2x80x9d U.S. Pat. No. 5,788,814, issued Aug. 4, 1998; Sun et al., xe2x80x9cElectrostatic Chucks,xe2x80x9d U.S. Pat. No. 5,858,099, issued Jan. 12, 1999; Pletcher et al., xe2x80x9cApparatus for Electrostatically Depositing a Medicament Powder Upon Predefined Regions of a Substrate,xe2x80x9d U.S. Pat. No. 5,714,007, issued Feb. 3, 1998; Sun et al., xe2x80x9cMethod of making pharmaceutical using electrostatic chuck,xe2x80x9d U.S. Pat. No. 5,846,595, issued Dec. 8, 1998; Sun et al., xe2x80x9cAcoustic Dispenser,xe2x80x9d U.S. Pat. No. 5,753,302, filed May 19, 1998; Sun, xe2x80x9cBead Transporter Chucks Using Repulsive Field Guidance,xe2x80x9d U.S. Pat. No. 6,096,368, issued Aug. 1, 2000; Sun, xe2x80x9cBead manipulating Chucks with Bead Size Selector,xe2x80x9d, U.S. application Ser. No. 09/047,631, filed Mar. 25, 1998; Sun, xe2x80x9cFocused Acoustic Bead Charger/Dispenser for Bead Manipulating Chucks,xe2x80x9d U.S. Pat. No. 6,168,666, issued Jan. 2, 2001; Sun et al., xe2x80x9cAC Waveforms Biasing For Bead Manipulating Chucks,xe2x80x9d U.S. Pat. No. 6,149,774, issued Nov. 21, 2000; Sun et al, xe2x80x9cApparatus for Clamping a Planar Substrate,xe2x80x9d Ser. No. 09/095,321, filed Jun. 10, 1998.; Poliniak et al., xe2x80x9cDry Powder Deposition Apparatus,xe2x80x9d U.S. Pat. No. 6,063,194, May 16, 2000; and xe2x80x9cPharmaceutical Product and Method of Making,xe2x80x9d Ser. No. 09/095,616, filed Jun. 10, 1998. Moreover, Sun et al., xe2x80x9cDevice For The Dispersal And Charging Of Fluidized Powder,xe2x80x9d filed concurrently herewith U.S. Pat. No. 6,063,194 describes various apparatuses and methods for charging, sizing and manipulating particles.
This invention addresses electrostatic chuck charge sensing, where because of the sensitive nature of the quantities to be measured, certain problems that arise from effects of ionic species and polarizable materials (e.g., water vapor, dust) in the vicinity of the particle contact surface where particles are to be attracted and retained.
Polarization occurs readily in many materials, arising from different atomic and molecular charge-shifting processes. Permanent dipole moments in molecules result in orientation polarization, which is only lost at high excitation frequencies, where molecules may not have enough time to reorient in response to a fast-changing electric field. Aside from the weak effect of distortion polarization arising from distortion of the positions of atomic nuclei by applied fields, there are also polarization effects arising from distortion of atomic electron distributions in response to electric fields, known as electronic polarization.
It is assumed here for simplification that dielectrics in the vicinity of the particle contact surface of the electrostatic chuck, or dielectrics that are used as part of the chuck structure are so-called Class A dielectrics, having a molecular polarizability which is linear, isotropic, and homogeneous. However, this invention is not limited to the examples given here, and may be practiced using chucks employing other than Class A dielectrics, where the molecular polarizability xcex1 is a tensor, and possibly a function of position inside the dielectric as well. Moreover, the invention is not limited by the various elements of theory recited here and elsewhere in this disclosure. The invention relates to the observation that a drift-resistant detection or sensing circuit (or multiple detection circuits) can be incorporated into an electrostatic chuck by using capacitance-based sensing of accumulated charge with respect to both a charged particle-attracting electrode, and an oppositely biased shield electrode that is appropriately configured and biased to yield the drift reduction. Applicants have set out their an estimation of the associated parameters and theory, but the invention exists and can be practiced based on appropriate empirical controls irrespective of such associated parameters and theory.
In Class A dielectrics, the vector electric polarization P resulting from a local electric field E is linear, where
P=xcex1Exe2x80x83xe2x80x83(1)
and xcex1 is a simple function of the applicable dielectric constant:
xcex1=∈0(Kxe2x88x921)Exe2x80x83xe2x80x83(2)
where ∈0 is the vacuum permittivity and K is the dielectric constant.
Electrostatic chuck designs and operation techniques using attraction electrodes or particle deposition electrodes to pick up and discharge particles can, under certain conditions, encounter voltage drift and measurement error when attempting to sense accumulated charge over the particle deposition electrode because the presence of ionic species, polarizable materials, or substrates having changing polarization, because the charge sensed is shifted to a value which is not proportional to or indicative of, the actual accumulated or deposited particles. When using DC (direct current) bias voltages on electrostatic chucks, unwanted charge shifting and migrating can cause measurement error. For example, a negatively biased electrode will attract positive ions from the air, while a positively biased electrode will attract negative ions from the air. At the same time, polarizable materials like water will be attracted separately to both positively biased and negatively biased electrodes, causing an unpredictable change in effective capacitance of the sensing electrode. Those phenomenon introduce voltage drift error when sensing minute amounts of accumulated particle electric charge, and affect uniformity of particle deposition from chuck to chuck, and from batch to batch. Preparation of dosage forms is thus made difficult because of quantity variations in particles deposited containing active ingredient.
It is important to keep in mind that manipulated charged particles in the vicinity of any conductive surface are subject to powerful electrostatic image forces. As a charged particle approaches any metal or conductive surface, such as a deposition electrode inside a powder dispenser or container, an image charge of opposite polarity will accumulate on that conductive surface. This happens when mobile charge carriers in the conductive surface are attracted by, or repelled by, the particle charge. This movement of charge in the conductive surface in response to a charged particle in the vicinity creates a potent image charge-induced holding force, or electrostatic image force. The electrostatic image force tends to make the particles highly attracted to, and usually later, in tight contact with, the conductive surface. It should be noted that dielectric beads and powder particles in stationary tight contact with a conductive surface have a tendency to keep their charge for long periods, often several days. With particles very close to (e.g., contacting) any conductor, the electrostatic image force generated tends to be greater than that due to any applied field originally used to accelerate the particles toward the electrostatic chuck, and can be on the order of hundreds of times the force due to gravity.
Generally, to attract and retain particles, the total electrical force Felec generated by the total electric field vector Etotal on a particle with mass m and charge q subject to gravitational acceleration g must be equal to or greater, overall, than the force of gravity, Fgrav, for the particle, so that particle may be accelerated toward one or more attraction electrodes:
Felec=Etotalqxcx9cFgrav=m gxe2x80x83xe2x80x83(3)
Upon applying a voltage to a deposition electrode (DE), a particle attraction field Ea may be established. This attraction field Ea can cause particles to be accelerated in the direction of, and subsequently retained by the electrode or an associated particle retention zone.
The total electric field vector, Etotal, results from a number of electric field components, by the principle of superposition. Typically, in the particle manipulation theatre, the total electric field at any point, Etotal, is the vector sum of any discrimination field Ediscrim applied between the electrostatic chuck and a distant mesh or other electrode or surface, such as a powder feed tube; any polarization field EP resulting from internal charge polarization inside powders or other bodies present in the particle manipulation theatre; any rejection or repulsion fields Er set up to discourage particle attraction in selected areas, or to repel particles, such as by applying a repulsive bias to one or more electrodes or conductive surfaces; any particle attraction fields Ea set up via an attractive bias applied to one or more powder deposition or attraction electrodes; and all electrostatic image fields Eimage set up by conductive surfaces on the electrostatic chuck or in the particle manipulation theatre:
Etotal=Ediscrim+EP+Er+Ea+Eimagexe2x80x83xe2x80x83(4)
Particle motions and interactions, or collisions with obstaclesxe2x80x94and each otherxe2x80x94inside a dispenser or container tend to randomize their motion, and this influences particle transport properties, as particles are accelerated toward intended electrodes or particle retention zones. However, in spite of this, the pull of a locally generated electrostatic image force, such as that generated by a charged particle in the vicinity of an attraction electrode, remains in force and is hard to defeat.
In the vicinity of the electrostatic chuck, with a charged particle at a distance d from any conductive surface in the chuck, the electrostatic image force, Fimage, due to the image charge can become, as the particle nears the chuck, is far more significant than the force Fa=Ea q generated by the bead attraction field Ea:
Fimage greater than  greater than Faxe2x80x83xe2x80x83(5)
Roughly, the dependence of the electrostatic image force at a distance d for a given charge q on a particle, is as follows, using Coulomb""s Law for stationary point charges:                               F          image                =                              q            ⁢                          ^              2                                            4            ⁢                          πϵ              0                        ⁢                          d              ⁢                              ^                2                            ⁢                              (                                  π                  ⁢                                      xe2x80x83                                    ⁢                                                                                    d                        particle                                            ⁢                                              ^                        3                                                              /                    6                                                  )                                      ⁢            ρ            ⁢                          xe2x80x83                        ⁢            g                                              (        6        )            
In the denominator, ∈0 is the vacuum permittivity; (xcfx80dparticle{circumflex over ( )}3/6) is the particle volume; xcfx81 is the particle mass density in kg/m3; and g is the acceleration due to gravity. This form gives the electrostatic image force in units of g. This electrostatic image force can become a potent force at short distances, but in practice the powder attraction field Ea is still needed to bring charged particles within its influence.
A variety of techniques may be used simultaneously to enhance electrostatic chuck effectiveness, and in particular, to enhance the accuracy and reproducibility of particle manipulations from origination to target electrodes or particle retention zones. These include use of periodic air or fluid flow provided acoustically by a conventional speaker. Such a speaker (not shown) can be in fluid communication with some part of the particle manipulation theatre, so that it may direct acoustic energy to unseat particles that are held by electrostatic image forces to dispenser surfaces, or during particle discharge at a desired target (e.g., a dosage form), to unseat beads held by electrostatic image forces to the chuck itself. It should be noted, however, that preferred apparatuses and methods of delivering particle to an electrostatic chuck for deposition include those described in Poliniak et al., xe2x80x9cDry Powder Deposition Apparatus,xe2x80x9d U.S. Pat. No. 6,063,194 and Sun et al., xe2x80x9cDevice For The Dispersal And Charging Of Fluidized Powder,xe2x80x9d filed concurrently herewith.
However, it is not possible generally to move unwanted ions or polarizable materials such as water vapor and dust away from particle sensing electrodes, and this causes measurement errors in spite of any particle placement accuracy obtained through the use of speakers, fluid flow, and the like.
It is therefore desirable not only to obtain high resolution, directed particle deposition sensing that overcomes the tendency of ionic species and polarizable materials to skew deposition sensing measurements, but also to provide a method that allows automated matrix motion operations that permit accurate, repeatable directed particle deposition sensing, without adversely affecting the attraction of particle to intended particle deposition electrodes and retention zones inside a particle manipulation theatre.
Other objects sought and achieved by the invention will become apparent upon reading of the specification. For example, it is a further object of the invention to employ a driving circuit that automatically subtracts all or most xe2x80x9cerrorxe2x80x9d charge induced by such ionic or polarizable materials, while allowing unfettered sensitive particle charge sensing to proceed. This, combined with certain improved chuck fabrication techniques, makes accurate and reproducible particle deposition sensing much easier to achieve.
In attracting and manipulating particles, electrostatic image charges, electric polarization, and particle mass and transport, play a role.
These problems are addressed by this invention using methods that reduce the error-producing effect of unwanted ionic species and polarizable materials in the vicinity of the particle contact when performing particle deposition sensing by measuring accumulate particle charge near a deposition electrode. This allows easier, more accurate and reproducible particle deposition sensing.
In one embodiment, the invention provides an electrostatic sensing chuck for attracting particles to a portion of a particle contact surface near a deposition electrode, the electrostatic sensing chuck comprising a pixel comprising: a deposition electrode (DE) for selectively establishing an attraction field (Ea) at the particle contact surface; a shield electrode (SE) oppositely biased with respect to the deposition electrode; a charge sensing circuit to measure charge accumulated on each of the deposition electrode and the shield electrode, wherein the charge sensing circuit subtracts a second charge it senses at the shield electrode from a first charge it senses at the deposition electrode, thereby determining accumulated charge at the deposition electrode balanced by accumulated charge at the shield electrode (of opposite polarity).
Alternatively expressed, the invention provides an electrostatic sensing chuck is provided for attracting powder near a deposition electrode (DE) on a particle contact surface (PCS) that is in the presence of at least one polarizable material, and for charge sensing the powder when attracted and retained near the deposition electrode. The electrostatic sensing chuck comprises a deposition electrode for selectively establishing an attraction field (Ea) at the particle contact surface; a shield electrode (SE) oppositely biased with respect to the deposition electrode, with the shield electrode positioned, sized and oriented with respect to the deposition electrode such that an electric charge distribution created by polarization in any polarizable material near the deposition electrode is matched at least in part by a similarly created electric charge distribution of opposite polarity or direction near the shield electrode. In this way, the sum of the respective charges in the electric charge distribution and in the similarly created electric charge distribution of opposite polarity tends toward zero. The shield electrode does not have to be immediately adjacent the deposition electrode. In another embodiment, the shield electrode can be positioned immediately adjacent the deposition electrode.
The invention includes an embodiment where this matching is accomplished in large part by having the effective surface area of the shield electrode (ASE) matched to the effective surface area of the deposition electrode (ADE). Preferably under this embodiment, the surface areas are adjusted as needed to achieve cancellation of drift or error. The chuck can further comprise a dielectric layer (D) positioned adjacent either the deposition electrode or the shield electrode. In another embodiment, the pixels comprise one or more backing electrodes (BE) are provided, sized, positioned and oriented to occupy an area which makes a projection onto the particle contact surface in a location not subtended or covered by the deposition electrode or the shield electrode. The one or more backing electrodes (BE) can be sized, positioned and oriented to allow adjust field strengths at the deposition or shield electrodes to increase error correction achieved subtracting the second charge. Alternatively, the chuck can further comprise a dielectric layer positioned between the backing electrode and either of the deposition electrode or the shield electrode. The deposition electrode and the shield electrode can optionally be coplanar.
The invention can comprise a driving circuit for driving and interfacing with the electrodes of the electrostatic sensing chuck, the driving circuit itself comprising: [a] a two wire AC coupled circuit, having a first wire and a second wire; [b] a Wheatstone bridge connected to the first and second wires of the AC coupled circuit, with the Wheatstone bridge having a low pole and a high pole for DC extraction, each of the high pole and low pole available for individual connection to the one of the deposition electrode and the shield electrode; [c] a sensing capacitor connected to either of the first and second wires of the AC coupled circuit; wherein the sum of the detected respective charges in the electric charge distribution and in the similarly created electric charge distribution of opposite polarity is balanced (for example, toward zero) to reduce sensing error or drift. Optionally, the AC coupled circuit comprises a shielded transformer having a primary winding, driven by an AC bias source and a secondary winding providing the first and second wire.
The invention also provides a method for depositing or transporting particles using an electrostatic sensing chuck, comprising: [a] applying a first potential to the deposition electrode of the electrostatic sensing chuck to establish an attraction field (Ea); [b] applying a second potential to the shield electrode oppositely biased with respect to the first potential, [c] attracting with an electric field established by the first potential and retaining particles to a region of the particle contact surface. Additionally the method can comprise: [d] ceasing particle deposition near the deposition electrode by reducing the first potential after sensing a set amount of accumulated particle charge using the sensing circuit.
Optionally, a third potential is applied to one or more backing electrodes (BE) to increase error correction achieved subtracting the second charge or to aid in balancing the sum of the respective charges in the electric charge distribution and in the similarly created electric charge distribution of opposite polarity.
Additionally, one can: [e] reduce the first potential applied to the deposition electrode; and [f] discharge the powder. Further, one can: [g] align the electrostatic sensing chuck with a desired location.
The invention also includes a method for reducing unbalanced error charge Qunbalanced, the method comprising: [a] applying a first potential to the deposition electrode of the electrostatic sensing chuck to establish an attraction field (Ea); [b] applying a second potential to the shield electrode oppositely biased with respect to the first potential; [h] adjusting at least one potential selected from the group of potentials comprising the first potential, the second potential, and a third potential applied to backing electrode (BE), so as to lower an unbalanced voltage drift Vdrift such that Qunbalanced=Cchuckxc2x7Vdrift, where Cchuck is an effective capacitance for the deposition electrode for the electrostatic sensing chuck. The step [h] can allow, for example, an unbalanced charge Qunbalanced that will tolerated of less than 20 microCoulombs.
Further provided is a method of operating an electrostatic chuck of claim A. 1 comprising: providing in the electrostatic chuck at least four pixels comprising particle retention zones with associated deposition electrodes, where at least four of the pixels are the charge-sensing pixels, which charge-sensing pixels are adapted to monitor deposition in each of four representative regions that, in total, define all particle collecting area of the electrostatic chuck; operating the electrostatic chuck to apply particles to the particle retention zones of the electrostatic chuck; removing or reversing particle attracting biases applied the deposition electrodes based on data provided by the charge-sensing pixels.
Additionally provided is a n electrostatic chuck operating in an atmosphere comprising: a first layer formed of a solid dielectric; and a second layer formed on the first layer comprising at least one deposition electrode with a deposition surface facing away from the first layer and, substantially separated from the deposition electrodes by atmosphere, at least one shield electrode with a deposition associated surface facing away from the first layer. Preferably, a hypothetical surface incorporating the deposition surfaces and the deposition-associated surfaces is planar or smoothly curved to smoothly conform with a flexible planar substrate [preferably without stretching the substrate].